PROJECT SUMMARY This is an application for an NIMH Exploratory/Developmental Research Grant Award (R21) entitled Electrical field and neuroimaging based prediction of ECT induced clinical and cognitive effects. In this application, Dr. Miklos Argyelan proposes a comprehensive plan for identifying predictive biomarkers for the clinical effects and side effects of ECT treatment. The plan aims to understand the neural mechanisms of treatment response in major depressive disorders by integrating functional neuroimaging with neuromodulatory bioelectric treatment approaches. The most effective approach for treatment-resistant depression (TRD) remains electroconvulsive therapy (ECT). Despite intensive research, however, the mechanism of action for ECT remains unknown, and currently no clinical or biological biomarkers exist to predict response. In patients with TRD undergoing a trial of ECT (with bilateral electrode placement), the proposed study will use both resting-state and electrical field modeling as applied to structural MRI scans, to examine the neural circuitry underlying clinical response and neurocognitive side effects. Patients will undergo MRI scanning at baseline and will be followed with clinical and cognitive scales for the course of ECT treatment. Results of this proposal may lead to biomarkers that will optimize treatment algorithms for mood disorders with higher efficacy and a lower cognitive side effect profile. Identifying target mechanisms would not only improve the current deployment of bioelectric approaches as part of a ?precision medicine? approach, but could also lead to the development of novel therapies. This line of research will be conducted in an environment with investigators who are recognized experts in functional neuroimaging (Miklos Argyelan, M.D.), ECT (Georgios Petrides, M.D.), electrical field modeling (Marom Bikson Ph.D.,), statistical approaches of multivariate data analysis (Todd Lencz, M.D.) and biomarkers studies in psychiatry (Anil K. Malhotra, M.D.). The culmination of these research activities will enhance our understanding of both the neurobiological underpinnings of mood disorders and the mechanism of action of ECT treatment. These results will open new possibilities how to administer ECT. At the end of the award period Dr. Argyelan plans to submit an R01 grant application to translate these novel findings into personalized neuromodulation.